The Effects of Parathyroid Extract on Renal Function in Man

(1)

The Effects of Parathyroid Extract on Renal

Function in Man

Howard H. Hiatt, David D. Thompson

J Clin Invest. 1957;36(4):557-565. https://doi.org/10.1172/JCI103454.

Research Article

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THE EFFECTS OF PARATHYROID EXTRACT ON RENAL FUNCTION IN MAN

By HOWARD H. HIATT 1 AND DAVID D. THOMPSON 2

(From theNational Instituteof ArthritisandMetabolic Diseases, National Institutes ofHealth, Public HealthService,U. S._{Department of Health,}Education and _{Welfare, Bethesda, Md.)}

(Submitted forpublication August 30, 1956; accepted December 13, 1956)

The evidence that parathyroid extract acts di-rectly onbone appearsconclusive(1-3). Whether the extract exerts an effect on the kidney, how-ever, has not been so convincingly answered. It

has long been known that an increase in urinary

phosphate follows the administration of

parathy-roid extract (4, 5), but the mechanism of the phosphaturia has not been clearly elucidated.

Although the osteoclastic action of parathyroid

hormone could effect an increase in urinary inor-ganic phosphate, it could not simultaneously pro-duce the hypophosphatemia observed in patients

withhyperparathyroidism. Inhibition by the hor-moneoftherenalmechanism for conserving

phos-phate, on the other hand, would account for both

arise inurinaryand a fall inplasmaphosphate. Our studies demonstrate that a

depression

of the maximal renal tubular reabsorptive capacity

for phosphate follows the administration of

para-thyroid extract, although in normal subjects pro-longed treatment is required before such an effect is demonstrable.

SUBJECTS AND METHODS

Forty studies were carried out in nine of the normal subjects, the three patients with post-thyroidectomy hy-poparathyroidism and the hyperparathyroid male de-scribed in the previous paper (6). The experimental procedures have been outlined (6).3 All of the experi-ments were performed with the patients in the post-absorptive state.

Four lots of commercial (Eli Lilly & Company) para-thyroid extract were used. Each lot was shown to be

1_{Present address:} _{Department of} _{Medicine, Harvard}

Medical School and Beth Israel Hospital, Boston, Mass. 2Present address: Department of Physiology, Cornell Medical College, New York, N. Y.

8The following abbreviations will be employed: GFR, glomerular filtration rate; RPF, effective renal plasma flow; CG., inulin clearance; CPAH, para-amino-hippurate clearance; Tm, maximal renal tubular transport rate; PTH, parathyroid extract; Ca, calcium; P, inorganic phosphate.

effective as demonstrated by a rise in serum Ca in at least one subject. Dosage is expressed in U.S.P. units, as assayed by the manufacturer. When given intrave-nously the hormone was usually administered over a periodof 4 to 8 minutes. For the more prolonged stud-ies it was given subcutaneously at 6 to 12 hourly in-tervals, except where otherwise indicated.

Tostudy theeffects of PTH onTmP,buffered sodium phosphate, pH 7.40,was infused until conditions ofrenal tubular saturation were assured. Simultaneous with the intravenous administration of PTH a sustaining in-fusion was begun containing, in addition to inulin and PAH, an amount of sodium phosphate calculated to maintain as constant as possible the elevated plasma P level. Thus, observations of the influence of PTH on TmP were permitted without the possible interference of rapidly changing plasma levels.

RESULTS

Acute

effects of intravenous parathyroid extract at

endogenous levels of plasma P

A rise in urinary phosphate occurred immedi-ately following the intravenous administration of 200 to 1,000 units of PTH both to normal (Figure 1) and to hypoparathyroid (Figure 2) subjects. Atypical study in a normal subject is outlined in Table I, while data from studies in three normal

subjects are summarized in Table II. In two of thenormalindividuals,C. H., and J. N., the rise in

urinaryP occurred as a result of an increase in fil-tered

P,

which in turn, was caused by an increase in GFR. Phosphate reabsorption was increased in one subject and unchanged in the other. In thethirdnormal individual, E. E., theincrease in

excreted P could be accounted for by a decrease in tubular reabsorption of P (Table II). No

changein serumcalcium wasobserved during the

2 to 4hoursfollowing the administration of PTH.

Flushing frequently followed the intravenous ad-ministration of PTH, and transient headache was an occasional complaint. A mild and brief

tachy-cardia often occurred, butno changes in tempera-tureorblood pressure wereobserved. There was

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HOWARD H. HIATT AND DAVID D. THOMPSON

.0 200UNITSgv

o

T

L 0.5

C')

0

>- 0.25

4

z

7AM 8 9 10 II ₁₂ 1PM 2 PM

TIME

FIG. 1. URINARY PHOSPHATE EXCRETION BEFORE AND FoLLowING THE INTRAVENOUS ADMINISTRATION OF 200 UNITS OF PARATHYROID EXTRACT TO R. H., A 24-YEAR-OLD NORMAL FEMALE

no evidence of sensitization or

resistance,

even in

subjects who received several injections over a

period oftwelve months.

Acute effects of intravenous parathyroid extract

under conditions of phosphate loading

Aswas noted atendogenous plasmaP

levels,

no

constant change in renal tubular

reabsorption

of Presultedfrom the

administration

ofPTH to

sub-jects receivingPinfusions (Table III). Ifin the

study summarized in Table III one selects two

periods with comparable levels of plasma P, e.g.,

the 6th, before the administration of PTH, and the7th, after PTHwas

given,

onenotes thatafter

PTH the excretion of P is

increased.

The risein

urinaryPis ascribableto anincrease infiltered P, the reabsorbed P

remaining

unchanged.

Similar

findings werenoted in ninestudies in five normal

subjects (Table IV). The levels of TmP

fol-lowing the administration of PTH did not differ

significantly

from those seen priorto the

adminis-tration of the hormone

(Figure 3).

D.

F.,

who

showed the greatest fall in TmP

following

PTH,

1.0 0

I

E

IL_0.

0

IL

z

7AM 8 9 10 II 12 1PM

TIME

FIG. 2. URINARY PHOSPHATE EXCRETION BEFORE AND

FOLLOWING THE INTRAVENOUS ADMINISTRATION OF 200 UNITS OF PARATHYROID EXTRACT To L. D., A 52-YEAR-0uD FEMALE WITH _{POST-OPERATIVE.}

HYPOPARATHYROID-was

unique

_among the

subjects

studied in that

spontaneous variationsof his TmP ofsimilar mag-nitudewere observed onoccasions when no medi-cation was

given.

With but one _exception a rise in GFR followed the intravenous administration

of

_PTH,

andonall occasions a

striking

rise in

re-nal

_plasma

flow was observed

_(Table

_IV).

In

almost all normal

_subjects

the rise in GFR was

adequate

to account for the observed increase in Pexcretion.

In the

hypoparathyroid

subjects,

on the other

hand,

the rise in

urinary

P which followed the

administration of PTH resulted notonly from an

increase in filtered

P,

but from a striking dimi-nution in the reabsorbed Paswell

(Table

V). A fall inTmP wasseenin all three

_{hypoparathyroid}

subjects, although

in A. W. a _{negligible decrease} inresponseto PTHwasobserved on oneoccasion

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TABLE I

EFFECTS OF INTRAVENOUS PARATHYROID EXTRACT ON RENAL FUNCTION

AT ENDOGENOUS PLASM PHOSPHATE LEVELS

ELAPSED _CPAll CIN PLASMA P PHOSPHATE

TIME _Ii.

_/m".1

_F&M/mi. FILTERED EXCRETED REABSORBED

Min. FM/mi.. FM/mi.. IM/iaS.

82-106 S35 122 1.01 123 8 1 S

106-123 SI 106 1.04 113 7 106

123-152 458 106 1.03 109 6 103

152-189 83 138 1.00 138 20 118

189-217 825 130 0.96 125 24 101

J.N., 22yewoldnormal male.

Sustaining inlisinfusionbegunat 51mnl.

1SS-160.1.,1000USP waits ofparathyroidextract i.v.

TABLE II

ACUTE EFFECTS OF INTRAVENOUS PARATHYROID EXTRACT AT ENDOGENOUS PLASMA PHOSPHATE LEVELS IN NORMAL INDIVIDUALS

Units CPAH CIN Plasma P _{PhlsplseveM/i}

Sublet ef ml/miu. ml/min. AM/mi Filtered EzSie Reabsrbed Extroct Before After Before After Before Ahf Before After Before After Befoe Aher

C.N. 800 550 674 121 145 1.12 127 136 184 2 1S 134 169

E.E. 800 620 930 130 131 1.08 1.06 140 139 3 18 137 121

J.N. 1000 502 832 112 134 1.03 0.98 115 131 7 22 106 109

TABLE III

EFFECTS OF INTRAVENOUS PARATHYROID EXTRACT ON RENAL FUNCTION DURING PHOSPHATE LOADING

lElpsed Urn

CPAH

CIN

P_Pl@a _Phosphate _PAI/min. 1|ia

mbldi:__

Time | Flow | P

ml/in

mI/min.

mi/mi..

UIM/mI

Fitrd Ecetd Rasre 0 lusli, PAH infusion bequn.

1 41- 59 5.45 538 142 1.09 155 4 151

2 59- 75 1 8.00 I 500 135 1.07 144 4 140

76 Inulin, PAH, buffered sodium phosphate infusion begun.

3

109-139

L890

543 140 2.16 302 92 210

4 139-170 5.00 502 142 2.52 358 152 206

5 201 -221 4.85 463 130 3.53 459 262 197

6 221-243 3.18 500 141 4.02 566 329 237

24 Maintenance inulil, PAH, phosphate infusion

_he"un.

1247-251 200 USP wnitsof _parwhroid extracti.v.

7 279 -301 j3.45 652 152 4.15 625 386 239

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Tic'L Itr

ACUTE EFFECTS OF INTRAVEOUS PARiTiYWROIDIETRACT ON INAL FUNCTION IN NORMALSUBJECTS

Units C__CPAN C~IN TaP

Dot _Sojebe of A Aftr Penatm Sewp Aftr. Pumtl Afts. Prese

___4Emtel/wi_.vJ~mb~i/wi.. ml/min. _Chm. M/Nd. p.M_/r. C.has

3/25/54 C.M. 200, 16. 6O.v i1n 104 .0 190 215 +13 4/ 6/54 C. H. 200 500 620 + 4 1'6 146 + 7 217 241 + 11

7/1t3/54 C.L Soo 761 865 "4. 1 ₁₅₁ ₁₆₄ _'4 ₉ ₁₃₈ ₁₄ ₊ _S

9/ 7/54 C.L' 500 56 610 b 44 13S 14 + 10 2X9 204 is

5/2S/54 E.L 900 62? 104 +6? 13S 15S* +13 l9 20 +23

6/10/54 .N 1000 475 M +S3 106 118 +11 177 15 11

6/22/54 LN. 1000 124 137 X10 176 16 + s

3/11/5U L. . 500 3W 6n 60 91 99 9 62 59 -.26

3/31/55 EP. SO0 S m41 + 96 118 + 99 12V +26

normal subjects occurred patients (Table VI).

The acute administrati cernible immediate effect potassium or on urinary

subjects.

Effects of prolonged trei extract

Hyperparathyroidism N

mal subjects on six occa

parathyroid patients by 1,800to4,500 units of e)

to 120 hours. In all sut

pophosphatemia, and an

cium and phosphate were Two subjects complainer

anorexia, polydipsia, pol

-.z250 7₂₀₀

z 0 o

F-150

w100

w

50

C0 0

MINUTES

FIG. 3. VARIATIONS IN I jECTS BEFORE AND FoLLow] MINISTRATION OF PARATHYR

I in the hypoparathyroid These symptoms, as' well as the chemical

abnor-malities rapidly disappeared after discontinuation ion of PTH had no dis- of the hormone.

t on plasma calcium 'or The hyperparathyroid state was characterized

r calcium in any of the by a depression'of TmP in-'both normal (Table

VIII) and hypoparathyroid (Table IX)

sub-jects. The fall in TmP ranged from 27 to 64per

atment with parathyroid cent below control levels (Table

X)'.

In W. R.

on one occasion (5/6/55) the TmP was reduced

was induced in five nor- byparathyroid extract to the level observed in the

Lsions and in two

_hypo-

only patient with spontaneous hyperparathyroid-the administration of ismstudied. The latter, a72-year-oldmale with a

tract over periods of60 plasma Ca of 14.05 mg. per 100 ml. and a plasma

)jects hypercalcemia, hy- Pof0.53 AMper ml. wasfound to have a TmP of increase in urinaryrcal, 26E*M per minute.

e observed (Table VII). The effect of the prolonged administration of d of mild skeletal :pain, parathyroid extract on C1,, and on CPAH, in con-Iyuria, and constipation. trasttotheresults in the acute studies, was

incon-stant (Table X).

Renal function studies were carried out in a

THYROIDEXTRACTim. Ihypoparathyroid patient in the untreated state

(plasma Ca, 7.10 mg. per cent; P, 1.42 b&M per

ml.), in an "isoparathyroid" state, following the dailyadministration of 100 units of extract for 5

days (plasma Ca, 10.05;P, 1.10), and ina

hyper-i_< - - parathyroid state, following the daily

adminis-SUB(2JCT0)S

tration of 900 units of extractfor 3

days (plasma

~.-4E.E(9

Otratio

of 90

&*E.EMOO

_Ca,

1290;

_P

0.68)o

_.

Average

TmP

values of

-*0D.(500 ) 170, 15Q and

70&uM

per_{minute, respectively,}were

found at these times (Figure 5). In a similar

I U

_Z

series of studiesin a secondhypoparathyroid

sub-30 W0 1t0

ject, B. C., a

progressive

towering of TmP with

'mP IN FIVa NoRMAL SUB-

increasing

doses of extract was

again

noted

ING THE INTRAVENOUS AD (TableXI). Ofinterestisthe fact that 100 units

0om EXTRACT of parathyroid extract daily for 3 days served to

I

_PARA

I_

-9_ 60 30 0

560

(6)

EFFECTS OF PARATHYROD ON RENAL FUNCTION

TABLE V

ACUTE EFFECTS OF PARATHYROID EXTRACT ON RENAL FUNCTION IN HYPOPARATHYROIDISM

ELAPSED PHOSPHATE

TIME CPAH CIN PLASMA P _FILTERED _EXCRETED _REABSORBED

MIN. ml/mi/mn. m/.m1n. PiM/Ml

N/in.

IN/min.

IN/mI.

77-. 97 345 90.0 2.26 181 79 102

97-116 316 73.0 2.60 190 96 94

116-136 315 75.5 3.00 226 116 110

159-192 711 840 2.80 235 177 58

192-216 625 90.0 2.57 231 183 48

LD., 52yewoldfemale, postopenrtiv.hypoporothyroldism. Coatinuousinfusion of bufferedsodIumphosphateiad ils.. 137-145min.,Praothyroidextract,(Lillyno.628857), 500 USPunits i.v.

lower B. C.'s plasma P and TmP without altering thelevel of plasma Ca. Hyperparathyroidism was

induced in this subject by intermittent intravenous administrationof extract. This wasthe only one

of the prolonged studies reported in hypopara-thyroidpatients in which PTHwasgiven by other

than the subcutaneous route. D. F. and W. R., two normal subjects, received three successive daily infusions, each containing 1,500 units of

extract, and each given intravenously over a

six-hour period. No effect on plasma Ca or P or on

TmP (measured 15 hours after the last infusion ofPTH) wasobserved. In W. R.,anequal

auan-tity ofthe same lot of hormone given in repeated

subcutaneous injections over a similarperiod

pro-duced marked hyperparathyroidism (Table VII).

DISCUSSION

Two explanations have been offered for the

in-crease in urinary phosphate usually observed

fol-lowing the administration of parathyroid extract. The evidence supporting these hypotheses, an in-crease in the load of phosphate filtered through

the kidney, on the onehand, and a diminution in

the tubular reabsorption of phosphate, on the

other,hasbeensummarized by Bartter (8). The 'The fall in CI3 in this subject in the hyperparathy-roid state was believed ascribable to mild congestive heart failure, a state known to be accompanied by a

reduced GFR (7). Digitalis, with which she had been treated for signs of failure noted one year previously,

had been omitted prior to the administration of

para-thyroidextract

rise in filtered phosphate has been ascribed to an

increase in glomerular filtration rate, to a rise

in plasma phosphate, orto both (9-11). Indeed, the demonstration that phosphaturia follows the administration to animals of formalin-inactivated (as assayed by its effect on serum calcium)

para-thyroid extract has been interpreted as indicating

that the observed increase in urinary phosphate is an artifact ascribable to some non-hormonal

componentofanexceedingly heterogeneous

prepa-ration (12).

Our data indicate that the phosphaturia seen

immediately following the intravenous adminis-tration of the extract to normal individuals is the result of an increase in GFR with a consequent

z 250

i

1200

z

0

1-CL .150

0

('

co 4

or

tW 100

W

I SO

4

CL))

aO

MINUTES

FIG. 4. CHANGES IN TMP FOLLOWING THE

ADMINIS-TRATION OF PARATHYROID EXTRACT TO THREE SUBJECTS

wrrt HYPoPARATHYROIDISm

IPARATHYROIDEXTRACT v.

_ ~~~~~~500U.S.P.

UNITS-SUBJECTS

I-o--NA.W.

o9---3oB.C.

90 60 30 0 30 s0 90 120

561

(7)

TABLE VI

ACUTE EFFECTS OF INTRAVENOUS PARATHYROID EXTRACT ON RENAL FUNCTION IN NYPOPARATHYROIDISM

Units CPAII CIN TaP

Doe Subject of Before After Percent Before After Percet 3.fee After rcenpt

Extract Mi/ala. ml/min. Chong*,emI/mim/mi. Chonge p/mi.. P.M/ai.. Champ

8/25/54 A.W. SOO 96 103 + 7 is1 142 -10 2/25/SS A.W. 500 498 852 + 71 108 113 + 5 137 75 -45

2/22/55 B.C. 500 230 418 + 75 63 69 + 10 SO - 49 3/9/55 L D. 500 325 668 + 102 75 87 + 16 Si -48

TABLE VII

EFFECTS OF PROLONGED ADMINISTRATION OF PARATHYROID EXTRACT ON PLASMA AND URINARY CALaWU AND PHOSPHORUS

Total Plosma Co Plsme P Urine Co Urine P

Subject Units of Hours of mg. percent MA/mI MM/Min. PAw.in.

Administration - -

-Extract Before After Before After Before After Befor Afbu

Notma_

C.H. 7/13/54 4000 60 9.80 13.50 1.23 1.02 9 52

W.R. 8/19/54 4500 72 10.02 13.90 0.96 0.73 23 s2

W.R. 5/ 6/55 4000 72 9.40 15.20 0.98 0.63 280 420 7 27

E.P. 3/31/55 2500 120 10.60 12.90 1.17 0.6 213 506 8 20

LB.11/22/54 2100 72 9.20 12.00 0.90 0.70 257 44 16 24

W.H 10/22/54 1800 66 .60 11.31 1.23 0.96 161 212 9 25

Hyporthyroid

A.W. 9/30/54 3000 % 7.10 12.90 1.42 06 3 9 0.9 11

B. C. 2/24/54 2500 60 LOS 11.95 1.35 0.74

TABLE VIII

RENAL EXCRETION OF PHOSPHATE BEFORE (A) AND AFTER (B)

ADMINISTRATION OF 1500 USP UNITS OF PARATHYROID EXTRACT DAILY FOR 3 DAYS

ELAPSED PHOSPHATE

TIME CPAH CIN PLASMA P _FILTERED _EXCRETED REABSORBED

Min. ml/min. ml/min. FM/ml. |SM/ri.. PM/min. PM/Min.

A 80- 109 570 100 2.43 243 104 139

109-139 580 102 2.74 279 143 136 139-169 555 106 3.05 324 181 143

B 183-222 684 124 2.36 29m 214 78

222-243 665 107 2.61 279 225 54

266-293 576 111 2.33 259 213 46

W.R.22 yearold normalmale.

Continuous infusion of buffered sodiumphosphateand vulii.

rise in filtered phosphate. In hypoparathyroid subjects the relative increase in phosphate

excre-tionis even more

striking,

for in such individuals

parathyroid extract produces not only a rise in

filtration rate, but a depression of tubular

(8)

TABLE IX

RENAL EXCRETION OF

PHOPHATE

BEFORE (A) AND AFTER

(B)

STRATICN OF

900

USP UNITS OF

PARATHYROID

EXTRACT DNLY FOR 3 DAYS

ELAPSED _____PHOSPHATE

TE CPH CIN PLASMA P FILTERED EXCRETED REABSORBED Min. Mlmn ml min )L/M.L//I.A . I&M/mIn. ILM/min.

A 16 -205 86 865 265 229 60 169

205 -232 95 86.0 3.17 2n 98 174 26529692 82.5 4.36 360 188 172

B 165--1 206 131 1.77 232 163 69

228-256 218 133 2.35 312 267 45

256-286 212 129 3.07 396 295 101

A.W.,37ywoldhypoporul yroidmle.

Co"ti;u

as

infusionof

hnuIi

mndbuffered sodium

phosphOte.

TABLE X

EFFECTS OF PROLONGED AMINISTRATION

taneous administration of extract, however, both

to normal and to hypoparathyroid subjects in-duces a state of hyperparathyroidism, character-ized by an invariable and striking diminution in

TmP. No effortwasmadetodetermine the mini-mal period of extract administration required be-foreatubular effect is demonstrable innormal

in-dividuals; sixty hours was the shortest duration

of an experiment involving the subcutaneous

ad-ministration of hormone, and a 31 per cent

de-crease in TmP was observed. Why the tubular

effect is more readily demonstrable in the

hypo-parathyroid than in the normal individual is

un-known, but this phenomenon may have a parallel

in the increased sensitivity to small amounts of thyroid noted in patients with myxedema (13). Of considerable interest is the fact that the

in-duced hyperparathyroid state in several of our

OF PARATHYROID EXTRACT ON RENAL FUNCTION

subjects wasnotaccompaniedbyarise in GFRor

inRPF. These observations strengthen the thesis that the factor in parathyroid extract exerting an

action on renal hemodynamics is distinct from

the hormonal principle(s) responsible for hyper-calcemia and a reduction in TmP. While our

data support the concept that the phosphaturia

seen in normal subjects immediately after the

in-travenous administration of PTH is not the result of changes in renal tubular transport of phosphate, they also demonstrate that under ap-.

propriate conditions tubular reabsorption of phos-phate is profoundly inhibited by the hormone. Similar findings have been noted in the dog by Handler and Cohn (14).

The fact that prolonged administration of the

extract is required to depress TmP in normal individuals raises the question as to whether the

Total

_oCfACPAH

CIN TmP

stki¢t o Before After Percent Before After Prcomi Befe Afer Peret

Ex|tracI Ml/min. ml/mill. Change mi /mi. Oange Al/Mwin. PMl/mie. O_pche

C.H.7/13/54 4000 60 550 763 + 39 135 151 + 12 200 138 -31

W. . 8/19/54 4500 72 585 728 + 24 113 121 + 7 122 63

-4a

W R.S/ 6/55 4000 72 558 568 +2 102 95 -7 81 29 _-i P.3/31/55 2500 120 537 430 -20 96 8s -11 110 64 -42 LB.11/22/54 2100 n 846 837 -1 136 131 -4 124 91 .27 W.K10/22/54 1800 46 904 889 -2 125 129 + 3 179 116 -3N A. W.9/30/54 200 n 157 200 + 96 129 +34 175n -59

LC 2/24/54 2SOO 60 236 232 -2 74 57 23 131 56 -57

(9)

TABLE XI

EFFECTS OF PARATHYRW

EUiRkf

SI YLPOPARATiYOiWSlA(BC.)

_e. Elmt ElepsTd Plow _. Plasm

Ear

_1.

_{.vwini..Fiberei}

_{_}

_Ex*_Folisrid_|E

2/9/55

Wms.

0 * S

X*t~ iCiem of W19*-wi,,PAN, id pGoo

89-121 6.85 -.40 _3.33 252 5 252 114 138

121_153 .07 3.73 234 '73.6 274 143 131

IS3_

-M 1.81 i"<too 222 a 161 12S

A.

237

1

n

1 139 132 2/14/55 50m.Wld 0 7.56 0.91

X4w 3dep X6 h-ComismossI.~slem of _Wim;'FIAN,

_pb.bsIH

_sad _o,

93_124 832 2.09 2.67 2" A*4.O 24 131 9

124-157

8821

94

265 b

. 244

1"

78

157 -187 9.40 La W.3 _S .3 277 194 a

los. j 259 83.4 248 I 8s

2/24/55 MEOs.q. 0 111.95 L74t1

12bkeSi.. 10 C_stleessiAusim.ofIsili, PAN.sdpbospv

in-25 3.41 2.57 1220 57.7 n148 9 I

20 -2413

51AS

3.02 225 1 l

1131

55

241-270 OI 9.03 32

252_SjS 51"

_17 62

___

I

it

123215.6

i

1161

hormone acts directly on the renal tubule. That

the hypercalcemia produced by the hormone is notresponsibleforthechange in tubulartransport

ofP is indicated by the demonstration thata rise in plasma Ca leads to an increase in the tubular

reabsorption of P

(15).

In addition, theprompt

and striking fall in TmP which follows the

intra-venous administration of

parathyroid

extract to

I-a

40

Is

0-0 100 200 300

PHOSPHATE FILTEREDAM/ MINUTE

400

FIG. 5. TUBULAR REABSORPTION OF PHOSPHATE AT

SEVERAL LvETs OF FITERED PHOSPHATE IN A

Hypo-PAATHYROID SUBJECTIN THE UNTREATED STATE, IN AN "ISOPARATHYROID" STATE, AND IN A HYPERPARATHYROID STATE

hypoparathyroid subjects strongly suggests a di-recteffectof the hormone on the renaltubule.

No manifestations of

hyperparathyroidism

were

observed in W. R. following the intravenous ad-ministration of 1500 units of extract over a

six-hour period on each of three successive days.

Whether the renal tubule and bone of the normal

individual must be constantly exposed to the ex-tract for an even more prolonged period of time

before achangein TmP or in calcium metabolism is demonstrable remains to be answered.

The demonstration of an action of PTH on the

kidney does not, of course, exclude an effect on

bone. Indeed, only by invoking an action of the

hormone at both sites can one satisfactorily

ex-plain the chemical aberrations characteristic of

patients

with hyperparathyroidism. It would ap-pear reasonable, then, to assume that the

secre-tion(s)

of the parathyroid alters metabolic proc-esses in bone, in kidney, and possibly even

else-where.

SUMMARY

1. The intravenous administration of parathy-roid extract results in aphosphate diuresis. Such

aneffect in normal subjects can generally be

ac-counted for by a rise in filtered phosphate

sec-ondary

toarisein

glomerular

filtrationrate

with-A.W. d' 37 YEARS

POST-OPERATIVEHYPOPARATHYROIDISM

* NoMEIArIe

o PARKiWOID EXTRACT100USPUNISS.C.00XS A * gm * C..DX

0 .

_ if ' ' o _~~

(10)

EFFECTS OF PARATHYROID ON RENAL FUNCTION

out any decreaseinphosphate Tm. In hypopara-thyroid individuals there is a diminution in the tubular reabsorption of phosphate as well as _an

increase in filtered phosphate.

2. Repeated subcutaneous injections of para-thyroid extract both to normal and to

hypopara-thyroid individuals lead to a diminution in the

maximal tubular reabsorptive capacity for

phos-phate.

3. The phosphaturia seen after the acute

ad-ministration of extract to normal individuals is

usually caused by an action of the extract on re-nal hemodynamics and is not

accompanied

by

hy-percalcemia.

Following

the

prolonged

adminis-tration ofparathyroid extract to normal individu-als, however, hypercalcemia is observed as well as a decrease in TmP, but without any constant

change in renal

hemodynamics.

ACKNOWLEDGMENT

We wish to express our gratitude to Misses Mary Margaret Brown and Doris Graves for their technical assistance.

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